Sickle Cell Disease Flashcards
Sickle Cell Disease: is a group of ________________ RBC disorders that most commonly affects the _______________ population. It results from a ________________ in the genes that encode hemoglobin.
inherited/genetic
African American
genetic mutation
autosomal recessive
What are problems with the red blood cells in Sickle cell disease:
- shortened life span 10-20 days
- unable to carry oxygen, less oxygen delivered throughout areas of body
- rbcs sickle/stick together in blood vessels
- a lot of complications in response to lack of oxygen to the tissues
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(HgbS) Hemoglobin S =
“sickle” shape, this causes RBCs to be rigid with a concave “sickle shape
Sickled RBCs burst (hemolyze) after ____
10-20 days, which causes anemia and fatigue. Have a much shorter life span. The bone marrow can not keep up with this rate of turnover for replacing these red blood cells. Patient becomes anemic.
normal RBCs have a lifespan of _____________
90-120 days
Irregularly shaped red blood cells are unable to _________
transport/carry oxygen effectivity. They stick together & get stuck, blocking smaller blood vessels (vascular occlusion) and causing many complications.
Symptoms of sickle cell disease develop _____________
2-3 months after birth. This is because a fetus and young infants have RBCs with fetal hemoglobin (HgbF), which blocks the sickling of RBCs. Fetal hemoglobin (HgbF) is protective.
HgbF:
fetal hemoglobin
HgbA:
normal adult hemoglobin
HgbS:
sickle shaped hemoglobin
Acute Complications of Sickle Cell Disease:
- vaso-occlusive crisis (VOC) also called Acute pain crisis
- Acute Chest Syndrome
- anemia
- cholecystitis
- infections
- stroke
-priapism - multiorgan failure
- spleen sequestration
Chronic Complications of Sickle Cell Disease:
- chronic pain
- avascular necrosis (bone death)
- pulmonary hypertension*
- renal impairment
-leg ulcers - gallstones
- pregnancy complications
- retinopathy
- priapism
vascular occlusion:
prevents oxygen from reaching the tissues, causing them to become ischemic. This can lead to different types of Sickle Cell Crisis.
vaso-occlusive crisis (VOC) also called Acute pain crisis:
- most commonly occurs in lower back, legs, hips, abdomen, and chest
- can last for days or weeks
- if their is pain in the chest and evidence of a pulmonary infection, then this is considered “Acute Chest Syndrome” which is life threatening and can lead to death
Due to the risk of acute stroke, females with Sickle Cell Disease SHOULD NOT use ___________
estrogen contraceptives. Only Progestin-only contraceptives, levonorgestrel intrauterine devices (IUDs) and barrier methods are preferred for contraception.
A healthy spleen has several physiologic roles including:
- removal of old or damaged red blood cells
- aid in immune function, making and storing white blood cells
- clearing some types of bacterial pathogens from the body, particularly encapsulated organisms: Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis
In Sickle Cell Disease, the spleen becomes fibrotic and shrinks in size due to repetitive sickling and infarctions. This causes functional ________
asplenia (decreased or absent spleen function)
Patients with Sickle Cell disease are at an increased risk for ________. They require immunizations and __________
- serious infections
- prophylactic antibiotics
Non drug treatment in Sickle Cell Disease:
Blood transfusions protect against many of the life threatening complications of SCD by providing RBCs with hemoglobin A.
Stroke, acute chest syndrome and severe anemia are acute complications that warrant treatment with ________
blood transfusions
When administering chronic monthly blood transfusions, the goal Hgb level should be no higher than _____________.
One of the risks of blood transfusions is ____________
10 g/dL post infusion
iron overload, which can lead to hemosiderosis (excess iron that impairs organ function)
The Only Cure for Sickle Cell Disease is ___________
bone marrow transplantation
Major drug classes used in SCD include:
- immunizations & antibiotics for __________
- analgesics for__________
-chelation therapy _____________
- to reduce infection risk
- controlling pain
- manage iron overload from blood transfusions
Droxia
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Dosage forms: capsule
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hydroxyurea
Class:
Indications: Sickle cell disease to reduce the frequency of acute pain crisis, episodes of acute chest syndrome, and the need for blood transfusions. Is indicated for adults with > than or equal to 3 moderate to severe pain crisis in one year, patients with severe or recurrent acute chest syndrome, chronic symptomatic anemia or disability. Use in all children > 9 months of age regardless of disease severity.
MOA: is a disease-modifying drug that STIMULATES the production of HgbF (fetal hemoglobin).
Dosage forms:
Dosing:
*Use IBW or TBW, whichever is less, when calculating daily dose.
*Round doses up to the nearest capsule size.
Max dose:
Boxed Warnings: *Myelosuppression (decreased WBCs and platelets),
malignancy (leukemia, skin cancer)
Warnings:
*Avoid Live Vaccines! since drug causes suppression
*Fetal toxicity, avoid in pregnancy (teratogenic)
Increased risk of pancreatitis, hepatotoxicity and peripheral neuropathy when used with antiretroviral drugs (especially didanosine & stavudine).
Side Effects:
increased LFTs, uric acid, BUN and SCr; mouth ulcers, N/V/D, alopecia, low sperm count (males),
Monitoring:
*CBC with differential every 2-4 weeks during treatment initiation and titration, then every 2-3 months once a stable dose is achieved. If toxicity occurs (ANC < 2000/mm3, platelets < 80000/mm3) hold hydroxyurea until the bone marrow recovers, then restart at a dose 5mg/kg/day lower.
Pearls/Notes:
*Contraception required during treatment AND after discontinuation (6 months for females and 12 months for males)
*Hazardous drug- cytotoxic, special handling required - wear gloves when dispensing and wash hands before and after contact. Capsules Should NOT be opened.
*Folic acid Supplementation is recommended to prevent macrocytosis
*Clinical response can take 3-6 months
Sunscreen should be used due to increased risk of skin cancer
Drug-Drug/Food interactions:
- Do NOT Use with pimecrolimus, tacrolimus and other drugs that cause myelosuppression (clozapine, deferiprone, leflunomide, natalizumab, tofacitinib)
Hydrea
class:
Indications:
MOA:
Dosage forms: capsule
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hydroxyurea
Class:
Indications: Sickle cell disease to reduce the frequency of acute pain crisis, episodes of acute chest syndrome, and the need for blood transfusions. Is indicated for adults with > than or equal to 3 moderate to severe pain crisis in one year, patients with severe or recurrent acute chest syndrome, chronic symptomatic anemia or disability. Use in all children > 9 months of age regardless of disease severity.
MOA: is a disease-modifying drug that STIMULATES the production of HgbF (fetal hemoglobin).
Dosage forms:
Dosing:
*Use IBW or TBW, whichever is less, when calculating daily dose.
*Round doses up to the nearest capsule size.
Max dose:
Boxed Warnings: *Myelosuppression (decreased WBCs and platelets),
malignancy (leukemia, skin cancer)
Warnings:
*Avoid Live Vaccines! since drug causes suppression
*Fetal toxicity, avoid in pregnancy (teratogenic)
Increased risk of pancreatitis, hepatotoxicity and peripheral neuropathy when used with antiretroviral drugs (especially didanosine & stavudine).
Side Effects:
increased LFTs, uric acid, BUN and SCr; mouth ulcers, N/V/D, alopecia, low sperm count (males),
Monitoring:
*CBC with differential every 2-4 weeks during treatment initiation and titration, then every 2-3 months once a stable dose is achieved. If toxicity occurs (ANC < 2000/mm3, platelets < 80000/mm3) hold hydroxyurea until the bone marrow recovers, then restart at a dose 5mg/kg/day lower.
Pearls/Notes:
*Contraception required during treatment AND after discontinuation (6 months for females and 12 months for males)
*Hazardous drug- cytotoxic, special handling required - wear gloves when dispensing and wash hands before and after contact. Capsules Should NOT be opened.
*Folic acid Supplementation is recommended to prevent macrocytosis
*Clinical response can take 3-6 months
Sunscreen should be used due to increased risk of skin cancer
Drug-Drug/Food interactions:
- Do NOT Use with pimecrolimus, tacrolimus and other drugs that cause myelosuppression (clozapine, deferiprone, leflunomide, natalizumab, tofacitinib)
Siklos
class:
Indications:
MOA:
Dosage forms: scored tablet
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hydroxyurea
Class:
Indications: Sickle cell disease to reduce the frequency of acute pain crisis, episodes of acute chest syndrome, and the need for blood transfusions. Is indicated for adults with > than or equal to 3 moderate to severe pain crisis in one year, patients with severe or recurrent acute chest syndrome, chronic symptomatic anemia or disability. Use in all children > 9 months of age regardless of disease severity.
MOA: is a disease-modifying drug that STIMULATES the production of HgbF (fetal hemoglobin).
Dosage forms:
Dosing:
*Use IBW or TBW, whichever is less, when calculating daily dose.
*Round doses up to the nearest capsule size.
Max dose:
Boxed Warnings: *Myelosuppression (decreased WBCs and platelets),
malignancy (leukemia, skin cancer)
Warnings:
*Avoid Live Vaccines! since drug causes suppression
*Fetal toxicity, avoid in pregnancy (teratogenic)
Increased risk of pancreatitis, hepatotoxicity and peripheral neuropathy when used with antiretroviral drugs (especially didanosine & stavudine).
Side Effects:
increased LFTs, uric acid, BUN and SCr; mouth ulcers, N/V/D, alopecia, low sperm count (males),
Monitoring:
*CBC with differential every 2-4 weeks during treatment initiation and titration, then every 2-3 months once a stable dose is achieved. If toxicity occurs (ANC < 2000/mm3, platelets < 80000/mm3) hold hydroxyurea until the bone marrow recovers, then restart at a dose 5mg/kg/day lower.
Pearls/Notes:
*Contraception required during treatment AND after discontinuation (6 months for females and 12 months for males)
*Hazardous drug- cytotoxic, special handling required - wear gloves when dispensing and wash hands before and after contact. Capsules Should NOT be opened.
*Folic acid Supplementation is recommended to prevent macrocytosis
*Clinical response can take 3-6 months
Sunscreen should be used due to increased risk of skin cancer
Drug-Drug/Food interactions:
- Do NOT Use with pimecrolimus, tacrolimus and other drugs that cause myelosuppression (clozapine, deferiprone, leflunomide, natalizumab, tofacitinib)
Endari
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L-glutamine
class:
Indications: FDA approved for adults and children > or = to 5 years old with Sickle Cell Disease.
- Is an amino acid shown to reduce acute complications of SCD (number of pain crises requiring parenteral analgesics, number and duration of hospitalizations and occurrence of acute chest syndrome).
MOA: Not fully understood, but it is thought to decrease oxidative stress, which can damage sickled RBCs.
Dosage forms: oral powder
Dosing:
- dosing is based on TBW
TBW < 30kg: 5 grams BID
TBW 30-65kg: 10 grams BID
TBW > 65kg: 15 grams BID
Max dose:
Contraindications:
Warnings:
Side Effects: constipation, flatulence, nausea, headache, pain (abdominal, extremities, back, chest), cough
Monitoring:
Pearls/Notes:
- Mix each dose in 8 oz of a cold or room temperature beverage (water, milk, or apple juice) OR 4-6oz of food (applesauce or yogurt); medication does not have to be completely dissolved prior to administration.
- better safety profile than hydroxyurea
Drug-Drug/Food interactions:
Oxbryta
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voxelotor
class:
Indications: FDA approved drug for patients age 4 years old and older with Sickle Cell Disease
MOA: Works by inhibiting hemoglobin S (HgbS) polymerization, which is the cause of SCD.
Dosage forms: tablet
Dosing:
1.5 grams once daily
(decrease dose if taking strong CYP3A4 inhibitors)
(increase dose if taking strong CYP3A4 inducers)
Max dose:
Contraindications:
Warnings:
hypersensitivity reactions, lab test interference with measurement of Hgb subtypes (A, F, S) by HPLC
Side Effects:
headache, fatigue, abdominal pain, diarrhea, nausea
Monitoring:
Pearls/Notes:
- can be given with or without hydroxyurea
- swallow tablets whole- do not crush, chew or cut tablet
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Adakveo
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crizanlizumab
class:
Indications: a monoclonal antibody that is FDA approved to reduce the frequency of vaso-occlusive crisis in Sickle Cell Disease.
MOA: works by binding to and inhibiting P-selectin, which is involved in adhesion of sickled erythrocytes to vessels (causing vaso-occlusion).
Dosage forms: injection
Dosing:
5mg/kg IV every 2 weeks for 2 doses THEN 5mg/kg every 4 weeks
Max dose:
Contraindications:
Warnings: infusion-related reactions
Side Effects: nausea, arthralgias, fever
Monitoring:
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Drug-Drug/Food interactions:
What happens when the red blood cells sickle to another and get stuck in the blood vessels?
patients can experience vasoocclusive crises. “acute pain crises”
- this can occur in a number of different organs
What are the functions of a healthy spleen? In someone without Sickle Cell Disease
- removes old and damaged red blood cells
- stores white blood cells and helps immune function
- clears bacteria from the body:
- Streptococcus pneumoniae
- Haemophilus influenzae
- Neisseria meningitidis
“Encapsulated bacteria”
functional asplenia:
“Develops in someone with sickle cell disease early on within 1-2 months of having disease”
- red blood cell sickling causes infarctions (ischemic attacks) of the spleen
- the spleen shrinks and becomes fibrotic (no longer functions)
- patients are at increased risk for infections
“complete loss of function of the spleen due to some medical condition”
Non-drug treatment for Sickle Cell Disease:
- Blood Transfusions (chronic monthly)
Supply HgbA
Maintain serum Hemoglobin < or = to 10g/dL
Risk: iron overload (which can cause hemosiderosis)
IF MONEY NOT AN ISSUE, THEN
- bone marrow transplantation
If someone with Sickle Cell Disease has a fever of 101.3 or greater then _________
should immediately seek medical attention. If an infection is possible then needs to be addressed quickly.
With blood transfusions in sickle cell patients, we are not aiming for a normal Hgb!! Because of the risk of ____
narrow range for hemoglobin in a patient with sickle cell disease is _______________
iron overload & hemosiderosis
narrow range for hemoglobin in a patient with sickle cell disease is less than or equal to 10g/dL
Drug treatment for Sickle cell disease:
Immunizations: “that target those 3 encapsulated organisms”
Routine Childhood Series
- Haemophilus influenzae type B (Hib)
- Pneumococcal conjugate (PCV13, Prevnar 13)
Additional Vaccines for functional asplenia:
- Meningococcal conjugate series + routine boosters
- Meningococcal serogroup B (Bexsero, Trumenba) “ at age 10 and older”
- Pneumococcal Vaccines - give one of the following: “at age 19 and older”
- PCV20 (Prevnar 20) x1 OR
- PCV15 (Vaxneuvance) x1dose then followed by PPSV23 (Peunomovax23) 8 weeks or more later.
Antibiotics:
Oral penicillin VK BID until age 5
Analgesics:
IV opioids for severe pain
(PCA patient-controlled analgesia common)
How do we dose hydroxyurea?
How do you calculate ANC?
neutrophils = Polys = SEGs = PMN polymorphular nuclear sites
When should we stop hydroxyurea in someone?
How do we dose L-glutamine?
TBW
Chelation therapy we use in patients with Sickle Cell disease to _______
remove excess iron stores from the body due to chronic blood transfusions
what is the antidote for iron toxicity?
Historically, deferoxamine an infusion for 8-12 hours
Now we have oral chelating drugs:
deferasirox (Exjade, Jadenu)
deferiprone (Ferriprox)
